Alzheimer's Disease (AD) is a major national health problem whose etiology and pathogenesis are not understood. The overall objective of the proposed research is to attempt to define the presence of a generalized cellular defect in extraneural tissue in familial and sporadic AD. Alteration in the physical state of erythrocyte-membrane proteins in familial versus sporadic AD will be assessed by electron-spin-resonance studies and correlated with freeze fracture electron-microscopic studies of erythrocyte membranes. The growth pattern, stages of mitotic duration, and ultrastructure of cultured AD skin fibroblasts before and after exposure to aluminum will be determined. Uptake of A1 at the ultrastructural level will be assessed in cultured AD fibroblasts by energy-dispersive x-ray analysis. Lymphocyte capping and phytohemagglutinin-ferritin labeling studies of lymphocytes will be performed to assess the dynamics of lymphocyte membrane function. The human leukocyte-antigen pattern of familial and sporadic AD will be performed. These studies have the potential of gaining insight into the molecular defect(s) in AD by use of easily obtainable, less complex extraneural tissue, and of leading to new approaches of studying this disease.